Although there have been many advances in the assessment and treatment of infections responsible for febrile neutropenia in cancer patients, it still remains a common complication of cancer therapy and accounts for the majority of chemotherapy-associated deaths. The ultimate goal of our interdisciplinary group of oncologists, infectious diseases experts, imagers, and biostatisticians is to conduct a large, prospective, multi-center trial to establish the utility and cost-effectiveness of PET/CT using the widely available glucose analogue [18F]fluoro-2-deoxy- D-glucose (FDG) in identifying sites of infection in cancer patients with persistent febrile neutropenia without an obvious identifiable source thus improving targeted therapy. The immediate goal of this Quick-Trials Exploratory Grant application is to conduct a pilot project in a smaller group of these patients to provide critical information that will support the concept, and aid in the design, of a larger multi-center clinical trial. The primary aim of this exploratory study is to perform FDG-PET/CT in approximately 130 cancer patients with persistent febrile neutropenia in whom an obvious source of infection has not been identified. Each suspicious site will be confirmed with pathologic ground truth whenever possible. The data will be evaluated to address the following questions, which are the sub-aims of this proposal: 1. How effective is FDG-PET/CT in identifying sites of infection in cancer patients with persistent febrile neutropenia without an obvious cause? 2. To what degree does FDG-PET/CT improve detection of sites of infection over CT alone? 3. What FDG-PET/CT imaging variables best predict the presence of infection at a specific site (e.g. standardized uptake value [SUV], concomitant abnormality on CT)? 4. Can the magnitude of FDG uptake as measured by an SUV at sites of infection predict the identity of the infective agent (bacterial vs. fungal vs. viral)? 5. Does the magnitude of uptake at sites of infection correlate with absolute neutrophil count? 6. Can a clinical scoring system be developed to identify a population of patients in whom FDG-PET/CT is likely to be most efficacious in identifying sites of infection? It is possible that FDG-PET/CT may be able to significantly change the management of the cancer patient with persistent febrile neutropenia resulting in improved clinical care; decrease the morbidity due to toxicities from certain toxic antibiotics; potentially decrease the cost of medical care by improved targeting of antibiotic therapy; and decrease days of hospitalization for these patients. All of these potential benefits may result in significant cost savings. FDG-PET/CT may be able to significantly change the management of cancer patients with persistent febrile neutropenia. FDG-PET/CT may be the most appropriate way to localize sources of occult and potentially life-threatening infections thus directly impacting therapy which may significantly impact the quality of life of very ill cancer patients by reducing morbidity and mortality. [unreadable] [unreadable] [unreadable]